Thioanisole ester based logic gate cascade to control ROS-triggered micellar degradation
Irene Piergentili (TU Delft - ChemE/Advanced Soft Matter)
Pepijn R. Bouwmans (Student TU Delft)
Luuk Reinalda (TU Delft - ChemE/Advanced Soft Matter)
R.W. Lewis (TU Delft - ChemE/Advanced Soft Matter)
Benjamin Klemm (Student TU Delft)
H. Liu (TU Delft - RST/Applied Radiation & Isotopes)
R. M. De Kruijff (TU Delft - RST/Applied Radiation & Isotopes)
Antonia Denkova (TU Delft - RST/Applied Radiation & Isotopes)
R Eelkema (TU Delft - ChemE/Advanced Soft Matter)
More Info
expand_more
Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.
Abstract
In certain tumor and diseased tissues, reactive oxygen species (ROS), such as H2O2, are produced in higher concentrations than in healthy cells. Drug delivery and release systems that respond selectively to the presence of ROS, while maintaining their stability in “healthy” biological conditions, have great potential as on-site therapeutics. This study presents polymer micelles with 4-(methylthio)phenyl ester functionalities as a ROS-responsive reactivity switch. Oxidation of the thioether moieties triggers ester hydrolysis, exposing a hydrophylic carboxylate and leading to micellar disassembly. At 37 °C, the micelles fall apart on a timescale of days in the presence of 2 mM H2O2 and within hours at higher concentrations of H2O2 (60-600 mM). In the same time frame, the nanocarriers show no hydrolysis in oxidant-free physiological or mildly acidic conditions. This logic gate cascade behavior represents a step forward to realize drug delivery materials capable of selective response to a biomarker input.
help_outline